CN100590125C - 作为a2b腺苷受体拮抗剂的黄嘌呤衍生物 - Google Patents
作为a2b腺苷受体拮抗剂的黄嘌呤衍生物 Download PDFInfo
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- CN100590125C CN100590125C CN03826411A CN03826411A CN100590125C CN 100590125 C CN100590125 C CN 100590125C CN 03826411 A CN03826411 A CN 03826411A CN 03826411 A CN03826411 A CN 03826411A CN 100590125 C CN100590125 C CN 100590125C
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- Prior art keywords
- diketone
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- compound
- methyl
- hydrogen
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2003/014085 WO2004106337A1 (en) | 2003-05-06 | 2003-05-06 | Xanthine derivatives as a2b adenosine receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
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| CN1771250A CN1771250A (zh) | 2006-05-10 |
| CN100590125C true CN100590125C (zh) | 2010-02-17 |
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|---|---|
| EP (1) | EP1622908B1 (pt) |
| JP (1) | JP2006515316A (pt) |
| CN (1) | CN100590125C (pt) |
| AT (1) | ATE403656T1 (pt) |
| AU (1) | AU2003249604B2 (pt) |
| CA (1) | CA2524778C (pt) |
| CY (1) | CY1108457T1 (pt) |
| DE (1) | DE60322748D1 (pt) |
| DK (1) | DK1622908T3 (pt) |
| ES (1) | ES2311759T3 (pt) |
| HK (1) | HK1092137A1 (pt) |
| MX (1) | MXPA05011860A (pt) |
| NZ (1) | NZ543416A (pt) |
| PT (1) | PT1622908E (pt) |
| SI (1) | SI1622908T1 (pt) |
| WO (1) | WO2004106337A1 (pt) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5044823B2 (ja) * | 2005-06-16 | 2012-10-10 | ギリアード サイエンシーズ， インコーポレイテッド | Ａ２ｂアデノシンレセプターアンタゴニストのプロドラッグ |
| ES2270715B1 (es) | 2005-07-29 | 2008-04-01 | Laboratorios Almirall S.A. | Nuevos derivados de pirazina. |
| ES2274712B1 (es) | 2005-10-06 | 2008-03-01 | Laboratorios Almirall S.A. | Nuevos derivados imidazopiridina. |
| CA2644996A1 (en) * | 2006-03-02 | 2007-09-13 | Cv Therapeutics, Inc. | A2a adenosine receptor antagonists |
| WO2009088518A1 (en) * | 2008-01-11 | 2009-07-16 | Cv Therapeutics, Inc. | A2b adenosine receptor antagonists for the treatment of cancer |
| US8871751B2 (en) | 2008-01-18 | 2014-10-28 | The Board Of Trustees Of The University Of Illinois | Compositions and methods relating to nuclear hormone and steroid hormone receptors including inhibitors of estrogen receptor alpha-mediated gene expression and inhibition of breast cancer |
| WO2009118759A2 (en) | 2008-03-26 | 2009-10-01 | Advinus Therapeutics Pvt. Ltd., | Heterocyclic compounds as adenosine receptor antagonist |
| WO2009157938A1 (en) * | 2008-06-26 | 2009-12-30 | Cv Therapeutics, Inc. | A2b adenosine receptor antagonists for treating cancer |
| WO2010103547A2 (en) | 2009-03-13 | 2010-09-16 | Advinus Therapeutics Private Limited | Substituted fused pyrimidine compounds |
| US8796290B2 (en) | 2009-11-09 | 2014-08-05 | Advinus Therapeutics Limited | Substituted fused pyrimidine compounds, its preparation and uses thereof |
| WO2012035548A1 (en) | 2010-09-13 | 2012-03-22 | Advinus Therapeutics Private Limited | Purine compounds as prodrugs of a2b adenosine receptor antagonists, their process and medicinal applications |
| WO2014143799A2 (en) * | 2013-03-15 | 2014-09-18 | Hydra Biosciences, Inc. | Substituted xanthines and methods of use thereof |
| ES2580702B1 (es) | 2015-02-25 | 2017-06-08 | Palobiofarma, S.L. | Derivados de 2-aminopiridina como antagonistas del receptor A2b de adenosina y ligandos del receptor MT3 de melatonina |
| US11370792B2 (en) | 2015-12-14 | 2022-06-28 | Raze Therapeutics, Inc. | Caffeine inhibitors of MTHFD2 and uses thereof |
| EP3618829B1 (en) * | 2017-05-05 | 2023-06-07 | Arcus Biosciences, Inc. | Quinazoline-pyridine derivatives for the treatment of cancer-related disorders |
| ES2975753T3 (es) * | 2018-03-05 | 2024-07-12 | Teon Therapeutics Inc | Antagonistas del receptor de adenosina y usos de los mismos |
| JP2022517978A (ja) | 2019-01-11 | 2022-03-11 | オメロス コーポレーション | がんを処置するための方法および組成物 |
| CN118459463B (zh) * | 2024-07-10 | 2024-09-06 | 山东中医药大学附属医院 | 一种化合物及其制备方法和治疗2型糖尿病的用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8510758D0 (en) * | 1985-04-27 | 1985-06-05 | Wellcome Found | Compounds |
| DE8817122U1 (de) * | 1988-12-22 | 1993-02-04 | Boehringer Ingelheim Kg, 55218 Ingelheim | Neue Xanthinderivate mit Adenosinantogenistischer Wirkung |
| JPH06102662B2 (ja) * | 1989-09-01 | 1994-12-14 | 協和醗酵工業株式会社 | キサンチン誘導体 |
| WO1995011681A1 (en) * | 1993-10-29 | 1995-05-04 | Merck & Co., Inc. | Human adenosine receptor antagonists |
| DE19535504A1 (de) * | 1995-09-25 | 1997-03-27 | Bayer Ag | Substituierte Xanthine |
| US6117878A (en) * | 1998-02-24 | 2000-09-12 | University Of Virginia | 8-phenyl- or 8-cycloalkyl xanthine antagonists of A2B human adenosine receptors |
| EP0956855B1 (en) * | 1998-04-24 | 2003-03-12 | K.U. Leuven Research & Development | Immunosuppressive effects of 8 substituted xanthine derivatives |
| US6545002B1 (en) * | 1999-06-01 | 2003-04-08 | University Of Virginia Patent Foundation | Substituted 8-phenylxanthines useful as antagonists of A2B adenosine receptors |
| KR100897219B1 (ko) * | 2001-06-29 | 2009-05-14 | 씨브이 쎄러퓨틱스, 인코포레이티드 | Ａ２ｂ 아데노신 수용체 길항제로서의 퓨린 유도체 |
| CN100467469C (zh) * | 2001-11-09 | 2009-03-11 | Cv医药有限公司 | A2b腺苷受体拮抗剂 |
| WO2003063800A2 (en) * | 2002-02-01 | 2003-08-07 | King Pharmaceuticals Research And Development, Inc. | 8-heteroaryl xanthine adenosine a2b receptor antagonists |
-
2003
- 2003-05-06 AT AT03817096T patent/ATE403656T1/de active
- 2003-05-06 MX MXPA05011860A patent/MXPA05011860A/es active IP Right Grant
- 2003-05-06 WO PCT/US2003/014085 patent/WO2004106337A1/en active Application Filing
- 2003-05-06 SI SI200331355T patent/SI1622908T1/sl unknown
- 2003-05-06 NZ NZ543416A patent/NZ543416A/en not_active IP Right Cessation
- 2003-05-06 CN CN03826411A patent/CN100590125C/zh not_active Expired - Fee Related
- 2003-05-06 ES ES03817096T patent/ES2311759T3/es not_active Expired - Lifetime
- 2003-05-06 PT PT03817096T patent/PT1622908E/pt unknown
- 2003-05-06 EP EP03817096A patent/EP1622908B1/en not_active Expired - Lifetime
- 2003-05-06 AU AU2003249604A patent/AU2003249604B2/en not_active Ceased
- 2003-05-06 DK DK03817096T patent/DK1622908T3/da active
- 2003-05-06 CA CA2524778A patent/CA2524778C/en not_active Expired - Fee Related
- 2003-05-06 DE DE60322748T patent/DE60322748D1/de not_active Expired - Lifetime
- 2003-05-06 JP JP2005500296A patent/JP2006515316A/ja active Pending
-
2006
- 2006-08-07 HK HK06108745.5A patent/HK1092137A1/xx not_active IP Right Cessation
-
2008
- 2008-10-27 CY CY20081101212T patent/CY1108457T1/el unknown
Non-Patent Citations (2)
| Title |
|---|
| 1,3-dialkylxanthine derivatives. jacobson k.drug development research,Vol.47 No.1. 1999 |
| 1,3-dialkylxanthine derivatives. jacobson k.drug development research,Vol.47 No.1. 1999 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004106337A1 (en) | 2004-12-09 |
| EP1622908B1 (en) | 2008-08-06 |
| DE60322748D1 (de) | 2008-09-18 |
| MXPA05011860A (es) | 2006-02-17 |
| CA2524778A1 (en) | 2004-12-09 |
| SI1622908T1 (sl) | 2008-12-31 |
| DK1622908T3 (da) | 2008-11-17 |
| CY1108457T1 (el) | 2014-04-09 |
| AU2003249604B2 (en) | 2011-06-30 |
| PT1622908E (pt) | 2008-11-14 |
| AU2003249604A1 (en) | 2005-01-21 |
| JP2006515316A (ja) | 2006-05-25 |
| ATE403656T1 (de) | 2008-08-15 |
| CA2524778C (en) | 2013-01-29 |
| CN1771250A (zh) | 2006-05-10 |
| HK1092137A1 (en) | 2007-02-02 |
| NZ543416A (en) | 2009-01-31 |
| EP1622908A1 (en) | 2006-02-08 |
| ES2311759T3 (es) | 2009-02-16 |
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